Acute Combined Cerebrolysin and Nicotinamide Administration Promote Cognitive Recovery Through Neuronal Changes in the Hippocampus of Rats with Permanent Middle Cerebral Artery Occlusion.

Stroke is one of the leading causes of disability worldwide, where the Hippocampus (HPC) is affected. HPC organizes memory, which is a cognitive domain compromised after a stroke, where cerebrolysin (CBL) and Nicotinamide (NAM) have been recognized as potentially therapeutic. In this study, we aimed to evaluate the efficacy of a combined administration of CBL and NAM in a rat stroke model. Male Sprague-Dawley rats (n = 36) were divided into four groups: saline (pMCAO - Saline), CBL (pMCAO + CBL), NAM (pMCAO + NAM), and experimental (pMCAO + CBL-NAM) (n = 9 per group). A permanent middle cerebral artery occlusion (pMCAO) was induced through electrocauterization of the middle cerebral artery, followed by the administration of CBL (2.5 ml/kg), NAM (500 mg/kg) or combined immediately after skin suture, as well as at 24, 48, and 72 h post-surgery. The rats were evaluated in the novel object recognition test; hippocampal infarct area measurement; reconstruction of neurons from CA1 for Sholl analysis; and, measurement of brain-derived neurotrophic factor (BDNF) levels near the infarct zone. Our findings revealed that the administration of CBL or NAM induced infarct reduction, improved cognition, and increased BDNF levels. Moreover, a combination of CBL and NAM increased dendritic intersection in CA1 pyramidal neurons. Thus, the combined administration of CBL and NAM can promote cognitive recovery after a stroke, with infarct reduction, cytoarchitectural changes in HPC CA1 neurons, and BDNF increase. Our findings suggest that this combination therapy could be a promising intervention strategy for stroke.

Association of the rs1966265 and rs351855 FGFR4 Variants with Colorectal Cancer in a Mexican Population and Their Analysis In Silico.

The aim of this study was to associate FGFR4 rs1966265 and rs351855 variants with colorectal cancer (CRC) in a Mexican population and to perform in silico analysis. Genomic DNA from 412 healthy individuals and 475 CRC patients was analyzed. In silico analysis was performed using the PolyPhen-V2, GEPIA, GTEx, and Cytoscape platforms. The GA genotype dominant model (GAAA) of rs1966265 and the AA genotype dominant and recessive models of rs351855 were identified as CRC risk factors (p < 0.05). CRC patients aged ≥ 50 years at diagnosis who consumed alcohol had a higher incidence of the rs351855 GA genotype than the control group (p < 0.05). Associations were observed between the rs1966265 GA genotype and patients with rectal cancer and stage III-IV disease. The rs351855 AA genotype was a risk factor for partial chemotherapy response, and the GA + AA genotype for age ≥ 50 years at diagnosis and rectal cancer was associated with a partial response to chemotherapy (p < 0.05). The AA haplotype was associated with increased susceptibility to CRC. In silico analysis indicated that the rs351855 variant is likely pathogenic (score = 0.998). Genotypic expression analysis in blood samples showed statistically significant differences (p < 0.05). EFNA4, SLC3A2, and HNF1A share signaling pathways with FGFR4. Therefore, rs1966265 and rs351855 may be potential CRC risk factors.

Environmental enrichment and cerebrolysin improve motor and cognitive performance in a rat model of stroke, in conjunction with an increase in hippocampal AMPA but not NMDA receptor subunits.

Stroke is a pathology related to the vascular system in the brain and it is one of the main causes of disability, representing a burden on public health. This lesion provokes a disorganization of sensory-motor and cognitive systems, the latter associated with hippocampal activity, a structure in which α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and NMDA N-methyl-D-aspartate (NMDA) receptors are important for the integration of information. Several molecules have been studied for their capacity to enhance recovery from a stroke, including cerebrolysin that could potentially be reinforced by environmental enrichment. Here, stroke was induced in 40 male rats and 24 h later, they were administered cerebrolysin (2.5 ml/kg), put in an environmentally enriched arena or given both treatments, for 10 days. Subsequently, motor functioning was assessed with the Bederson test and the cognitive domain was assessed through novel object recognition. Hematoxylin/eosin staining was then used to assess the infarct size, and AMPA-GRIA1 and NMDA-R1 subunits in the hippocampus were measured by ELISA. In motor and cognitive performance, the administration of cerebrolysin and environmental enrichment enhanced recovery. Moreover, the infarct size decreased in all the groups that received a treatment, but an increase occurred in AMPA-GRIA1 only in experimental group regarding to control group, while NMDA-R1 had no differences. These results suggest that cerebrolysin and environmental enrichment could act in synergy to recover after a stroke, leading to a smaller infarct area and the presence of more AMPA-GRIA1 subunits in the hippocampus of experimental group. These data encourage further studies in which neurorehabilitation approaches can be combined with cerebrolysin administration to treat the motor and cognitive symptoms of stroke.

Gene expression in multiple sclerosis during pregnancy based on integrated bioinformatics analysis.

BACKGROUND: The modulation of the activity disease in patients with Multiple Sclerosis (MS) that occurs during pregnancy is a helpful model which could provide insight into central disease mechanisms and facilitate treatment. Therefore, the aim of the study was to identify differentially expressed genes in-silico to perform biological function pathway enrichment analysis and protein-protein interaction from pregnant women with MS. METHODS: Transcriptome data were obtained from the Gene Expression Omnibus (GEO) database. We selected the microarray dataset GSE17449. The gene expression dataset contains the data of mononuclear cells from four different groups sought, including seven healthy women (H), four healthy pregnant women (HP), eight women with multiple sclerosis (WMS), and nine women nine months pregnant with multiple sclerosis (PMS). The GSEA software was employed for enrichment analysis, and the REACTOME database was used for biological pathways. The protein-protein interaction (PPI) network was plotted with STRING. The databases used to identify the connection of DEGs with different signaling pathways were KEGG and WIKIPATHWAYS. RESULTS: We identified 42 differentially expressed genes in pregnant women with MS. The significant pathways included IL-10 signaling pathway, ErbB2 activates, the hemoglobin complex (HBD, HBB, HBA1, AHSP, and HBA2), IL-17 signaling pathway (LCN2 and MMP9), antigen processing and presentation, and Th17 cell differentiation (HLA-DQA1), Rap1 signaling pathway (ID1), NOD-Like receptor signaling pathway (CAMP and DEFA4), PD-L1 Signaling, Interferon gamma signaling (MMP9 and ARG1), Neutrophil degranulation (CAMP, DEFA4, ELANE, CEACAM8, S100P, CHI3L1, AZU1, OLFM4, CRISP3, LTF, ARG1, PGLYRP1, and TCN1). In the WIKIPATHWAYS set, significance was found Vitamin B12 metabolism (TCN1, HBB, and HBA2), and IL-18 signaling pathway (S100P). CONCLUSION: This study can be used to understand several essential target genes and pathways identified in the present study, which may serve as feasible targets for MS therapies.

Genomic instability in people living with HIV.

The increased life expectancy of people living with HIV (PLWH) receiving antiretroviral treatment (ART) has transformed HIV infection into a chronic disease. However, patients may be at risk of accelerated aging and the accumulation of cellular damage, which may trigger the development of cancer. We evaluated genomic instability in HIV-positive individuals with different viral loads receiving antiretroviral treatment (ART) and in HIV ART-naïve individuals. We included 67 participants divided into four groups: group 1 (n = 24) HIV patients receiving reverse-transcriptase inhibitors (tenofovir/ emtricitabine/ efavirenz and abacavir/ lamivudine/ efavirenz), group 2 (n = 22) HIV patients receiving protease inhibitors combined with other antiretroviral drugs (tenofovir/ emtricitabine with ritonavir/ atazanavir or lopinavir/ ritonavir, and darunavir/ ritonavir/ raltegravir), group 3 (n = 13) HIV ART-naïve patients, and group 4 (n = 8) healthy individuals (controls). Nuclear abnormalities in buccal mucosal samples (micronuclei, binucleated cells, nuclear buds, karyorrhexis, karyolysis, and pyknosis) were quantified. Simultaneously, blood samples were taken to quantify CD4+, CD8+, and HIV viral load. There was a significant age difference between HIV ART-naïve patients and receiving ART groups. Infection time was longer in HIV patients with ART than in ART-naïve patients. There were no differences in sex, smoking, alcohol consumption, or number of micronucleated cells between the study groups. We found higher frequencies of binucleated cells and nuclear buds in HIV patients, HIV ART-naïve, and HIV ART patients compared to the control group. We found a positive correlation between nuclear buds and CD4/CD8 ratio in the HIV ART-naïve group. In conclusion, PLWH showed increased genomic instability. The CD4/CD8 ratio affects the numbers of nuclear buds and binucleated cells. These findings are pertinent to mechanisms of damage and possible strategies to mitigate carcinogenesis in PLWH.

[Total antioxidant capacity of the diet of pregnant women in the Community of Madrid]. / Capacidad antioxidante total de la dieta de las mujeres gestantes de la Comunidad de Madrid.

INTRODUCTION: Introduction and objective: pregnancy is a stage of life with high nutritional vulnerability and increased levels of maternal oxidative stress. Total antioxidant capacity (CAT) identifies the protective effect of a balanced diet rich in foods of plant origin with antioxidant activity. The aim of this study was to relate CAT with dietary intake and body mass index (BMI) in pregnant women in the Community of Madrid. Methods: a cross-sectional, comparative study was conducted in 89 pregnant women and 61 healthy women of reproductive age. Age, place of origin, weight, height, BMI, macronutrient and micronutrient intake, and dietary CAT by food frequency were recorded; CAT was classified as desirable (≥ 19,301.0 µm/g) or undesirable (< 19,301.0 µm/g); the statistical analysis, including χ², Student's t-test or Mann Whitney U-test, was made using the SPSS program v.23. Results: differences were found in caloric profile, intake of antioxidant micronutrients, and dietary CAT (p < 0.05). Mean CAT in pregnant women was 23,163.0 ± 10,829.0 µm/g, whereas in non-pregnant women it was 25,916.0 ± 9,703.0 µm/g (p = 0.035). Pregnant women with a desirable CAT (56.2 %) preferred to consume fruits and vegetables, and 65.6 % of non-pregnant women preferred bread, pasta and cereals (p = 0.02). Hand fruit, citrus fruits, green leafy vegetables, and tomato were preferentially consumed by both groups. In pregnant women, poor nutritional status, overweight, and obesity rates of 36.0 % were found versus 28.0 % in non-pregnant women (p < 0.001). Conclusion: the BMI of pregnant women is not related to dietary CAT or the relatively low consumption of antioxidant components.

INTRODUCCIÓN: Introducción y objetivo: el embarazo es una etapa de la vida con alta vulnerabilidad nutricional y aumento de los niveles de estrés oxidativo en la madre. La capacidad antioxidante total (CAT) identifica el efecto protector de la dieta equilibrada, rica en alimentos de origen vegetal con actividad antioxidante. El objetivo de este estudio fue relacionar la CAT con la ingesta dietética y el índice de masa corporal (IMC) en mujeres gestantes pertenecientes a la Comunidad de Madrid. Métodos: se realizó un estudio transversal comparativo de 89 mujeres gestantes y 61 mujeres sanas en edad reproductiva. Se registraron la edad, el lugar de origen, el peso, la estatura, el IMC, la ingesta de macronutrientes y micronutrientes, y la CAT dietética por frecuencia alimentaria; la CAT se clasificó como deseable (≥ 19.301,0 µm/g) y no deseable (< 19.301,0 µm/g); el análisis estadístico, con la prueba del χ², la prueba de la t de Student o la prueba de la U de Mann Whitney, se realizó de acuerdo con la normalidad de las variables en la población estudiada. Se utilizó el programa SPSS, versión 23. Resultados: se encontraron diferencias en el perfil calórico, la ingesta de micronutrientes antioxidantes y la CAT dietética (p < 0,05). La CAT promedio en las gestantes fue de 23.163,0 ± 10.829,0 µm/g, frente a 25.916,0 ± 9.703,0 µm/g en las no gestantes (p = 0,035). Las gestantes con CAT deseable (56,2 %) preferían consumir frutas y verduras, mientras que el 65,6 % de las mujeres no gestantes preferían el pan, la pasta y los cereales (p = 0,03). La fruta de mano, los frutos cítricos, las verduras de hoja verde y el tomate eran consumidos preferentemente por ambos grupos. En las mujeres gestantes, en cuanto al estado nutricional deficiente, la tasa de sobrepeso y obesidad fue del 36,0 %, frente al 28,0 % entre las no gestantes (p < 0,001). Conclusión: el IMC de las mujeres gestantes no está relacionado con la CAT dietética ni con el relativo bajo consumo de componentes antioxidantes.

Association of metabolic syndrome with low birth weight, intake of high-calorie diets and acanthosis nigricans in children and adolescents with overweight and obesity. / Asociación del síndrome metabólico con bajo peso al nacimiento, consumo de dietas hipercalóricas y acantosis nigricans en escolares y adolescentes con sobrepeso y obesidad.

OBJECTIVE: The theory of fetal programming suggests that low birth weight (LBW) predisposes to greater food intake and increases the chance of overweight and obesity, which are in turn associated to conditions such as metabolic syndrome (MS) and acanthosis nigricans. The study objective was to ascertain whether an association exists between MS, LBW, intake of high-calorie diets, and acanthosis nigricans in children and adolescents with overweight or obesity. MATERIAL AND METHODS: A case-control was conducted on 100 children who attended the overweight and obesity outpatient clinic of the OPD Hospital Civil de Guadalajara "Fray Antonio Alcalde". Subjects were stratified in groups with and without MS based on the criteria of the International Diabetes Federation for children aged less than 16 years. Data on LBW, intake of high-calorie diets for 24-hour dietary recalls (average 2 days a week), and acanthosis nigricans (Simone criteria) were obtained by questioning the parents. Frequencies and logistic regression were calculated using SPSS version 22. RESULTS: The results show that 82% of children and adolescents were obese and 18% overweight, and 73% had MS. MS was associated to LBW (OR: 4.83 [95% CI: 1.9-12.47]), high-calorie diets (OR:136.8 [95% CI: 7.7-2434]), and acanthosis nigricans (OR: 1872 [95% CI: 112.9-31028]). CONCLUSIONS: In children and adolescents with overweight and obesity, LBW, high-calorie diets, and acanthosis nigricans are associated to a higher probability of MS.

SERINC as a Restriction Factor to Inhibit Viral Infectivity and the Interaction with HIV.

The serine incorporator 5 (SERINC5) is a recently discovered restriction factor that inhibits viral infectivity by preventing fusion. Retroviruses have developed strategies to counteract the action of SERINC5, such as the expression of proteins like negative regulatory factor (Nef), S2, and glycosylated Gag (glycoGag). These accessory proteins downregulate SERINC5 from the plasma membrane for subsequent degradation in the lysosomes. The observed variability in the action of SERINC5 suggests the participation of other elements like the envelope glycoprotein (Env) that modulates susceptibility of the virus towards SERINC5. The exact mechanism by which SERINC5 inhibits viral fusion has not yet been determined, although it has been proposed that it increases the sensitivity of the Env by exposing regions which are recognized by neutralizing antibodies. More studies are needed to understand the role of SERINC5 and to assess its utility as a therapeutic strategy.

HIV Drug Resistance in Antiretroviral-Naive Patients in Mexico After 10 Years: Is There a Difference?

The aim of this study was to compare the extent of resistance to antiretroviral (ARV) drugs among the population in Mexico before and after 2005. The mutations and drug resistance database of Stanford University were used for analyzing drug resistance tests that had been performed on HIV treatment-naive patients. The sequences obtained were divided into group 1 (isolated in 2002-2003) and group 2 (isolated in 2010-2014). Both groups showed 14% similarity in resistance mutations. In both groups, mutations in N88D protease inhibitor were identified, D67N and T69D were found for nucleoside reverse transcriptase inhibitors (NRTIs), and K103N was found for non-nucleoside reverse transcriptase inhibitors. In both groups, the resistance to ARV drugs was 7.4%. Both groups showed resistance to nelfinavir, efavirenz, and nevirapine. The prevalence of resistance to ARV therapy remained stable from 2002 to 2014. However, a marked reduction in resistance to NRTIs was observed for the same period.

The Neuroprotective Effect of Erythropoietin in Rat Hippocampus in an Endotoxic Shock Model.

BACKGROUND: Sepsis is characterized by an early systemic inflammation in response to infection. In the brain, inflammation is associated with expression of pro-inflammatory cytokines (e.g. tumor necrosis factor-α, interleukin-1ß and interleukin-6, among others) that may induce an overproduction of reactive oxygen and nitrogen species. The constitutive expression of cytokines in the brain is low, but may be induced by various stimuli, including lipopolysaccharide, which causes neuronal damage. Erythropoietin, among other effects, acts as a multifunctional neurotrophic factor implicated in neurogenesis, angiogenesis, vascular permeability, and immune regulation in the central nervous system. In an experimental model of endotoxic shock, we studied the neuroprotective capacity of erythropoietin in the rat hippocampus and compared with melatonin, a neurohormone with an important antioxidant and immunomodulatory effect. METHODS: In 21-day-old male Wistar rats divided into eight groups, we administered by intraperitoneal injection lipopolysaccharide, erythropoietin, melatonin, or combinations thereof. The hippocampus was dissected and morphological (histological analysis) and biochemical (cytokine levels) studies were conducted. RESULTS: The number of dead neuronal cells in histological sections in groups treated with lipopolysaccharide was higher compared to the erythropoietin group. There was a greater decrease (70%) in interleukin-1ß concentrations in rats with endotoxic shock that received erythropoietin compared to the lipopolysaccharide group. CONCLUSIONS: The neuronal cell loss caused by endotoxic shock and interleukin-1ß levels were reduced by the administration of the hematopoietic cytokine erythropoietin in this experimental model.

Riesgo de trastornos alimentarios y perfil antropométricos en modelos profesionales de México / Risk of eating attitudes and anthropometric profile among professional fashion models of Mexico

Objective: The aim of this study was to compare the risk of Eating Disorders Behaviour (EDB), and its anthropometric profile, physical activity and alimentary intake between Mexican fashion models (FM) and control women Methods: We included 50 FM and 50 control women, of the same social group, all over 18 years old, from Guadalajara, Mexico, matched by age. We evaluated the risk of EDB with the Eating Attitudes Test (EAT-26); the anthropometric measures were taken according to the criteria of the International Society for the Advancement of Kinanthropometry (ISAK), 24-hour recall to estimate energy intake and physical activities. Results: The risk prevalence of EDB was 10% for both groups. The mean and standard deviation of the percentage of body fat in FM was 22,4±2, lower than in the controls (27,8±4, p<0.001). There were no differences in anthropometric measurements in women with and without risk of EDB, except in the weight (FM without risk of EDB 56,3±3 kg and 59,9±3 kg with risk of EDB (p<0.02). Caloric intake in women with risk of EDB reduced was 1094±208 kcal in FM versus 1269±435 kcal in control woman. Conclusion: The anthropometric measurements, alimentary intake and previous history of eating disorders, suggests that FM of Mexico are a vulnerable population for eating disorder.

Objetivo: Comparar el riesgo de trastornos de la conducta alimentaria (TCA), perfil antropométrico, actividad física e ingesta alimentaria entre las mujeres mexicanas dedicadas al modelaje profesional (MP) con mujeres control. Métodos: Se incluyeron 50 MP y 50 mujeres controles, del mismo grupo social, mayores de 18 años, de Guadalajara, México, pareadas por edad. Se evaluó el riesgo de TCA con el test de Trastornos de Actitudes Alimentarias (EAT-26), se tomaron las medidas antropométricas de acuerdo a los criterios de la International Society for the Advancement of Kinanthropometry (ISAK). Se estimó el consumo de energía utilizando el recordatorio de 24 horas y se registró la práctica de actividades físicas. Resultados: La prevalencia de riesgo de TCA fue 10% para ambos grupos. La media y desviación estándar del porcentaje de grasa corporal en las MP fue 22,4±2,5 menor al de las controles (27,8±4,9) (p<0.001). No hubo diferencias en la medidas antropométricas en las mujeres con y sin riesgo de TCA, excepto en el peso de las MP de 56,3±3,1 kg sin riesgo de TCA y 59,9±3,6 en las con riesgo de TCA (p<0.02). La ingesta alimentaria se encontró reducida en las mujeres con riesgo de TCA con respecto a las sin riesgo, con 1094,2±208,3 kcal versus 1269,8±435,0 kcal en las MP y controles respectivamente. Conclusión: Las medidas antropométricas, la ingesta alimentaria y la historia previa de trastornos de la alimentación, sugiere que la MP de México es una población vulnerable para trastornos de la alimentación.

Volume-of-interest assessment of oncologic response using 18F-FDG PET/CT: a phantom study.

UNLABELLED: The aim of this study was to evaluate the volume-of-interest (VOI) technique in the measurement of volume radioactivity and in the differentiation of necrotic sites from residual tumor activity in a phantom. METHODS: PET/CT was performed on a phantom filled with (18)F-FDG solution at different concentrations. The VOI was quantified in 2 sessions to evaluate the VOI measurements as a function of activity concentration in the phantom. Software was used to build the VOI, determine the volume radioactivity of the cylindric inserts (cm(3)), and compare them with their real volumes. The VOI technique was also used to discern the mixed distribution of regions of (18)F-FDG activity from cold regions that represent areas of necrosis without tumor activity. RESULTS: Volumes measured with the VOI technique were similar to the actual volumes of cylinders in the phantom (no statistical differences; P > 0.05 after t test analysis). The diameter of cold inserts correlated positively with the percentage of visualization (P < 0.01); in both sessions, it was possible to visualize 100% of the 12.7-, 11.1-, and 9.5-mm cold rods. CONCLUSION: VOI technique has shown great potential for evaluating volume radioactivity and differentiating hot and cold regions in a phantom; clinical studies should be performed with this technique to evaluate its utility.

Antioxidant activity of tryptophan in rats under experimental endotoxic shock.

Tryptophan (TRP), the precursor of the scavenger or immunomodulator molecules melatonin (MLT) and picolinic acid, can be found in the diet; and could be an alternative nutritional supplement used to regulate the immune response in the generation of free radicals. In an experimental model, the systemic administration of lipopolysaccharide (LPS), to promote the synthesis of pro-inflammatory cytokines, reactive oxygen species, and antioxidant enzymes, was performed on adult female, pregnant and lactating rats fed with a diet of TRP content (0.5mg/100g protein). Lung tissue was evaluated for levels of the products of lipoperoxidation (LPO's), malonaldehyde (MDA) and 4-hydroxy alkenals (4-HDA); nitrites (NO2), glutathione peroxidase (Gpx) enzyme activity, and the serum concentration of interferon-gamma (IFN-gamma), which were measured in the following groups: control (CTRL), LPS, MLT, TRP, LPS plus MLT (LPS+MLT), and LPS plus TRP (LPS+TRP). Results showed that the lung tissue levels of MDA and 4-HDA in the LPS+TRP group were significantly lower than in the TRP group. Statistically significant differences were not observed in nitric oxide levels among the groups LPS+MLT and LPS+TRP compared to the group under endotoxic shock (LPS). The Gpx enzyme activity was modified in the LPS+MLT vs the LPS group, but the difference was not statistically significant. The LPS+MLT group showed a smaller serum concentration (98%) of IFN-gamma than the LPS group. Statistically significant differences were not observed among the animals of the LPS+TRP and the LPS groups.

Depression and its correlation with in patients pain in the rheumatology service of a Mexican teaching hospital.

The depressive symptoms are associated with chronic pain in this study. A cross-sectional study was performed. A visual analog scale was used to register pain intensity. Depressive symptoms were measured using the Center of Epidemiological Studies (CES-Dr) scale as modified by Eaton and reviewed for use in the Mexican population. The study included 245 patients, with a mean age of 46 years, 86.1% of whom were female. The prevalence of some degree of depression was 55.1%. Patients with fibromyalgia had the highest prevalence of symptoms of depression (78.38%) and major depression (29.73%). Stepwise multiple regressions indicated that the best model (r2 = 0.26) to predict the CES-Dr score included the global pain score (P < 0.0001) and education level (P < 0.004). The Cronbach's alpha of the CES-Dr was high (alpha = 0.888). There was moderate correlation (r = 0.442), P < 0.0001 of the CES-Dr numeric score with the intensity of global pain.